The aim of this work was to compare different procedures for the serodiagnosis of human infections with the lymphocytic choriomeningitis (LCM) virus and to single out those which are both reliable and practicable. By the use of 46 sera from as many persons who had undergone infection with this virus either some time in the past or very recently and of 26 control sera, seven methods were evaluated. For making a rapid diagnosis soon after infection, determination of antibody by the immunofluorescence procedure appears to be the method of choice. Of equal reliability, though less easy to perform, is demonstration of sensitizing antibody by a plaque reduction assay, this procedure having the additional advantage of detecting antibody many years after infection, probably for life. For the demonstration of neutralizing antibody, three of four methods which were analyzed in this study gave the expected information, two employing mice, one employing cell cultures for the determination of residual infectivity. Neutralizing antibody was found to appear relatively late after infection and cannot, therefore, be recommended for the demonstration of seroconversion early in convalescence. This antibody, however, persists for many years, presumably lifelong, and is well suited to detect infections with this virus if they have occurred in the more distant past. Based on previous observations by ourselves and others, as well as on the work reported here, the complement fixation test appears to be of little value for the serological diagnosis of infection with LCM virus.